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Elamipretide Reverses Heart and Muscle Aging Without Resetting the Biological ClockLongevity & Aging

Elamipretide Reverses Heart and Muscle Aging Without Resetting the Biological Clock

Elamipretide (ELAM), a mitochondria-targeted peptide, was given for 8 weeks to young (5-month) and old (24-month) male and female C57BL/6J mice. Aged mice treated with ELAM showed reduced frailty accumulation, improved cardiac strain and ejection fraction, and better skeletal muscle fatigue resistance—especially in females. Despite these functional gains, RNA sequencing and DNA methylation arrays found no statistically significant changes in epigenetic or transcriptomic biological age in most groups. Pathway analysis did reveal pro-longevity gene expression shifts, including upregulated fatty acid metabolism and oxidative phosphorylation and downregulated inflammation. The findings suggest functional tissue improvements can be decoupled from molecular age reversal.

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